Activation of I(2)-imidazoline receptors may ameliorate insulin resistance in fructose-rich chow-fed rats.
Agmatine, an endogenous ligand of imidazoline receptors, was employed to screen the effect on insulin resistance in rats induced by a diet containing 60% fructose. Single intravenous (i.v.) injection of agmatine sulfate for 30min decreased the plasma glucose concentrations in a dose-dependent manner from 0.5mg/kg to 3mg/kg in rats received 4-week fructose-rich chow without an alteration of systolic blood pressure. The plasma glucose lowering action of agmatine (1mg/kg, i.v.) was abolished by the pretreatment with BU224 (1mg/kg, i.v.) at sufficient dosage to block I(2)-imidazoline receptors. In addition, the value of glucose-insulin index, the areas under the curve of glucose and insulin during the intraperitoneal glucose tolerance test, showing an index of in vivo insulin sensitivity was reversed by the same treatment with agmatine in fructose-rich chow-fed rats; this action was also blocked by BU224. Our results suggest that activation of I(2)-imidazoline receptor to improve insulin action on glucose disposal can be considered for targeting glucose metabolism under insulin-resistant state.
Ko
Wen Ching
WC
Department of Surgery, Mackay Memorial Hospital and Mackay College of Nursing and Technology, Taipei City, Taiwan.
Liu
I-Min
IM
Chung
Hsien-Hui
HH
Cheng
Juei-Tang
JT
D000376:Agmatine / Q000627:therapeutic use*; D000704:Analysis of Variance; D000818:Animals; D019540:Area Under Curve; D001522:Behavior, Animal; D001786:Blood Glucose / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000503:physiopathology; D004032:Diet; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005632:Fructose / Q000008:administration & dosage; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use; D054755:Imidazoline Receptors / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D008024:Ligands; D008297:Male; D051381:Rats; D017208:Rats, Wistar
C105826:BU 224; D001786:Blood Glucose; D007093:Imidazoles; D054755:Imidazoline Receptors; D007328:Insulin; D008024:Ligands; D005632:Fructose; D000376:Agmatine